The present application relates to a semiconductor structure and more particularly to a semiconductor structure that can be used for single molecule real time DNA sequencing applications. The semiconductor structure of the present application includes a photodetector, a zero waveguide module and semiconductor devices integrated on a same semiconductor substrate.
Knowledge of DNA sequences has become indispensable for basic biological research, and in numerous applied fields such as diagnostic, biotechnology, forensic biology, virology and biological systematics. The rapid speed of sequencing attained with modern DNA sequencing technology has been instrumental in the sequencing of complete DNA sequences, or genomes of numerous types and species of life, including the human genome and other complete DNA sequences of many animal, plant, and microbial species.
DNA sequencing is a process of determining the precise order of nucleotide within a DNA molecule. DNA sequencing includes any method that is used to determine the order of the four bases, i.e., adenine, guanine, cytosine and thymine, in a strand of DNA. The advent of rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery.
In some DNA sequencing processes such as, for example, the Sanger method, DNA polymerase has been used as a sequencing engine; DNA polymerase is any of various enzymes that function in the replication and repair of DNA by catalyzing the linking of nucleotides in a specific order, using single-stranded DNA as a template. In such technologies, single DNA molecule detection is required. Some existing single DNA molecule detection techniques are limited to low nanomolar concentrations, in order to reduce background fluorescence or other nucleotides that may be present in solution. At higher concentrations (which are typically required for DNA polymerase implementation), the detection volumes of prior art microscope systems are flooded with hundreds or thousands of labeled molecules. This creates high background noise level which makes it impossible to detect individual fluorophores.
DNA sequencing approaches that circumvent the aforementioned problem by, for example, step-wise addition of base-labeled nucleotides followed by washing, scanning and removal of the label, severely limit the capabilities of the polymerase.
To overcome the above problems, a single molecule real time DNA sequencing technology which enabled the observation of natural DNA synthesis by a DNA polymerase as it occurs was developed by Pacific Biosciences. See, for example, the publication to Eid et al. entitled “Real-Time DNA Sequencing from Single Polymerase Molecules”, Science, Vol. 323, 2, Jan. 2009. This single molecule real time DNA sequencing technology includes the use of an apparatus that contains a multiplex zero mode waveguide chip, an optical system, a light source, electronics and a detector. The optical system, detector, electronics and light source employed in such technology are separate components from the multiplex zero mode waveguide chip.
The implementation of separate components in single molecule real time DNA sequencing technology increases the cost of such a process and can reduce the speed and sensitivity of DNA sequencing. As such, there is a need for developing an apparatus for single molecule real time DNA sequencing technology which avoids the drawbacks mentioned above.